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Am J Hum Genet DOI:10.1016/j.ajhg.2012.10.016

Disruption of a large intergenic noncoding RNA in subjects with neurodevelopmental disabilities.

Publication TypeJournal Article
Year of Publication2012
AuthorsTalkowski, ME, Maussion, G, Crapper, L, Rosenfeld, JA, Blumenthal, I, Hanscom, C, Chiang, C, Lindgren, A, Pereira, S, Ruderfer, D, Diallo, AB, Lopez, JPablo, Turecki, G, Chen, ES, Gigek, C, Harris, DJ, Lip, V, An, Y, Biagioli, M, MacDonald, ME, Lin, M, Haggarty, SJ, Sklar, P, Purcell, S, Kellis, M, Schwartz, S, Shaffer, LG, Natowicz, MR, Shen, Y, Morton, CC, Gusella, JF, Ernst, C
JournalAm J Hum Genet
Date Published2012 Dec 07
KeywordsAdolescent, Alternative Splicing, Base Sequence, Chromosome Breakpoints, Chromosomes, Human, Pair 11, Chromosomes, Human, Pair 2, Developmental Disabilities, Female, Gene Order, Humans, Lymphocytes, Molecular Sequence Data, Mutation, Neural Stem Cells, RNA, Long Noncoding, Translocation, Genetic

Large intergenic noncoding (linc) RNAs represent a newly described class of ribonucleic acid whose importance in human disease remains undefined. We identified a severely developmentally delayed 16-year-old female with karyotype 46,XX,t(2;11)(p25.1;p15.1)dn in the absence of clinically significant copy number variants (CNVs). DNA capture followed by next-generation sequencing of the translocation breakpoints revealed disruption of a single noncoding gene on chromosome 2, LINC00299, whose RNA product is expressed in all tissues measured, but most abundantly in brain. Among a series of additional, unrelated subjects referred for clinical diagnostic testing who showed CNV affecting this locus, we identified four with exon-crossing deletions in association with neurodevelopmental abnormalities. No disruption of the LINC00299 coding sequence was seen in almost 14,000 control subjects. Together, these subjects with disruption of LINC00299 implicate this particular noncoding RNA in brain development and raise the possibility that, as a class, abnormalities of lincRNAs may play a significant role in human developmental disorders.


Alternate JournalAm. J. Hum. Genet.
PubMed ID23217328
PubMed Central IDPMC3516594
Grant ListHD065286 / HD / NICHD NIH HHS / United States
GM061354 / GM / NIGMS NIH HHS / United States
K99MH095867 / MH / NIMH NIH HHS / United States
K99 MH095867 / MH / NIMH NIH HHS / United States
R33 MH087896 / MH / NIMH NIH HHS / United States
R33MH087896 / MH / NIMH NIH HHS / United States
P01 GM061354 / GM / NIGMS NIH HHS / United States
R21 HD065286 / HD / NICHD NIH HHS / United States